Autoimmune disease — when the body turns on itself

Four million Britons have an autoimmune disorder, many of them women. Scientists are asking why

The Times

Peta Bee

Gerry Gajadharsingh writes:

“About time too, as all clinicians will know the incidence of “autoimmune problems” seems to have significantly increased over the past few years. The research below suggests that 4 million Britons now have an autoimmune problem, increasing at a rate of 9% a year. There are about 80 classified autoimmune conditions and about 75% of people with autoimmune conditions are women. Autoimmune means the body is attacking itself, the actual manifestation of the condition probably depends on the genetic predisposition of the patient. There is something about the patients’ lifestyle, environment, exposure to viruses, bacteria, parasites etc, immune system robustness, how their body and mind deal with “stress” and its effect on the autonomic nervous system that either switches on or off particular genes resulting in the presenting condition. It’s called epigenetics.

The research below explores the potential mechanisms as to why autoimmune conditions affect vastly more women than men. As always, I suspect it is an interplay of various factors and research really needs to focus on methodologies that explore multiple variables if we are really going to fundamentally help patients.”

Inflammation underpins most disease processes, adopting a pattern of eating that reduces inflammation can often be helpful. Eating the right mix of protein, fats and carbohydrates to provide us with the substrates and chemical messengers that our body needs for health is critical.

Understanding how our autonomic nervous system works and how we can improve our autonomic function can also be really helpful.

Realising the things both we as individuals and society are doing to our immune systems, affecting it negatively, will become better understood and accepted during the next few years. That is assuming people brave enough to stick their head above the parapet are given a chance to express their ideas without the vitriol and trolling that seems to be around these days.”

When it’s working well the immune system is a tour de force of disease resistance, battling to protect us against viruses, bacteria and any perceived threat to our health. But what happens when it goes awry? The prevalence of autoimmune disorders — in which the immune system turns on itself and mistakenly attacks healthy tissue — has increased sharply in recent decades. An estimated four million Britons now have one of these often debilitating and generally lifelong conditions, which are responsible for chronic inflammation and other serious symptoms.

Many of the 80 recognised autoimmune conditions — including type 1 diabetes, coeliac disease, psoriasis, rheumatoid arthritis, Crohn’s disease and multiple sclerosis (MS) — are spiralling and experts fear they will reach a scale of epidemic proportions. A report published in November by Connect Immune Research, a group of medical research charities including the British Society for Immunology and the MS Society, said that these “rapidly rising rates of autoimmune conditions” cost the UK billions. The prevalence of some autoimmune conditions, it said, was increasing by as much as 9 per cent a year.

Karen Addington, the UK chief executive of JDRF, the leading global organisation funding type 1 diabetes research, says that the “alarming and unexplained rise in autoimmune conditions among the UK population is causing pain, difficulty and lost opportunities in work and life”. A confounding factor is that an estimated 75 per cent of those who have an autoimmune condition diagnosed are women.

While research is under way to explain the sudden prevalence, and why women are disproportionately affected, theories are plentiful. “We’ve seen an increase in the ratio of women to men with many autoimmune conditions and we don’t really understand the reasons why this is the case,” Susan Kohlhaas, the director of research at the MS Society, says. “There could be environmental factors involved and there are genetic factors as autoimmune diseases can run in families, and in collaboration with other organisations we are embarking on investigations to find out more.”

A Swedish study published in the Journal of the American Medical Associationlast year showed that, in men and women, having a stress-related condition can increase the risk of autoimmune disease. Others have suggested that changes in the human microbiome — the ecosystem of microbes that live mostly in the gut and are thought to help to control our immune systems — may be contributing. Rachel Byng-Maddick, a consultant rheumatologist at the Bupa Cromwell Hospital, says that bacteria involved in gum disease are associated with rheumatoid arthritis, which “means flossing and good oral health are important in terms of prevention”.

Among the most intriguing theories about why women are so disproportionately affected came in a paper published in the journal Trends in Genetics this month. In what she dubbed the “pregnancy-compensation hypothesis”, Melissa Wilson, an evolutionary biologist at Arizona State University, suggested that the placenta was at the root of the reason that women’s immune systems are more prone to backfiring. Her theory is that, as hunter-gatherers, women — like all placental mammals — evolved to carry offspring for much of their reproductive life and that their immune systems became super-strong to protect them.

“It was not unusual for women to have 10 or 12 babies and to start having them at a young age,” Wilson says. “And the female body evolved to cope with those demands, with the placenta effectively sending messages to down-regulate the maternal immune system during pregnancy so that the foetus is not rejected.” But turning down the immune system too much brings other risks, such as the threat of bacteria and viruses that could damage an unborn infant. “So it became a compensatory situation with some give and take so that the maternal body was still protected. A woman’s immune system became primed to defend them in anticipation of pregnancy.”

What about when those multiple pregnancies don’t happen? Women in the UK now have an average of 1.9 children, a record low, according to the Office for National Statistics. According to Wilson’s theory, it’s this trend that has resulted in some women’s immune systems going haywire, seeking out anything to attack, including a healthy body. “Until the last century or so a woman’s immune system expected to be managing a placenta,” she says. “It’s only in the last 100 years that we’ve changed our pregnancies and our environment and it could be that now the placenta doesn’t have that kind of exposure, things have started to go wrong.”

She does not propose that women should have multiple pregnancies to avoid autoimmune disease. “Pregnancy can be risky in itself and women’s immune systems have evolved to mean they have lower rates of cancer than men,” Wilson says. “But the discovery could herald a new framework for testing how best autoimmune conditions can be treated.”

For the next phase of her research, Wilson hopes to analyse data from the UK Biobank to find out whether women with a greater number of children have lower rates of autoimmune disorders. “We also want to see if having pregnancies later or earlier in life makes any difference to the prognosis,” she says. “Our aim is to look at the full reproductive history of women and to see if there are any pathways that allow their immune systems to respond in different ways at different stages of their lives.”

She and her colleagues will also look at the protective role of female hormones. “We know that different types of oestrogen have different effects on the body,” Wilson says. “It is the kind called oestriol, only produced during pregnancy, that is protective against autoimmune disease.”

It has long been accepted that during the second half of pregnancy, when the placenta produces oestriol, women with autoimmune diseases have reduced relapses from autoimmune conditions. This protection during pregnancy has been observed in female patients with psoriasis, MS and rheumatoid arthritis. It has led scientists to think that oestriol could be a potential treatment for the disorders. A 2015 study at the University of California, published online in Lancet Neurology, showed that taking the hormone as well as their conventional medications helped to reduce relapses in patients with MS.

“What we want to find out is whether timing of pregnancies has an effect and if it matters at what age you have children,” Wilson says. “If we discover that earlier pregnancies offer greater protection, then it could mean you simply get a shot of oestriol at age 13 and you are better protected against autoimmune conditions.”

Her work is part of a whole range of studies investigating the gender bias, including studies funded by the MS Society that are investigating the role of specific immune cells during pregnancy. “Researchers are trying to identify immune cells that are active or inactive during pregnancy,” Kohlhaas says. “If we can pinpoint those it would really help advance our understanding.” Different stages of a woman’s reproductive life also warrant more study, she says. “There are fewer children with many autoimmune conditions, but the menopause and later life is really under-researched and it will be very interesting to see if the significant hormonal changes then play a role.”

What really matters in terms of future treatment options is the interplay between these and so many other factors. “Some people are genetically more susceptible to autoimmune disease if exposed to environmental triggers,” Byng-Maddick says. “Bacterial infections, hormones, diet, obesity, smoking and the Epstein-Barr virus can all be implicated in autoimmune function and they could be the reason for higher rates of disorders in women and lower rates in men. As yet we don’t know, but all of the new research is promising and brings hope.”